Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

Abstract   We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15–2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.     

The Effect of Reduced Somatosensation on Standing Balance: A Systematic Review

The objective of this review is to identify and review publications describing the impact of reduced somatosensation on balance. Based on knowledge of the association between specific somatosensory loss and deterioration of balance, conclusions can be made about role of somatosensation in standing balance.A systematic literature review is presented in which publications from the years 1993 through 2007 were searched in Medline and Embase. Medical Subject Headings (MESH) terms and free text words (related to balance, somatosensory loss, and lower limb) were used to perform the searches. Fifteen articles were selected for detailed review based on predetermined inclusion criteria, and three of the included articles described the effect of experimentally reduced somatosensation on balance in healthy subjects. Ten of the articles described balance in diabetic neuropathy (DN). The last two included articles described balance in Charcot-Marie-Tooth (CMT) disease type 1A (CMT1A) or type 2 (CMT2).The literature indicates that the tactile sensation is reduced in DN, CMT1A, and CMT2 and when the plantar surface of the feet was hypothermically anesthetized. Joint motion sensation seems to be impaired in patients with DN, and passive joint position sensation appears to be reduced in healthy subjects with anesthesia of ankle and foot from prolonged ischemia. This reduced somatosensation seems to have a negative effect on balance in patients with DN and CMT2; however, this appeared not to be the case in patients with CMT1A and in healthy subjects.     

蛋白质组学在皮肤科的研究进展

蛋白质组学是研究细胞内所有蛋白质及其动态变化规律的科学,近年来它被广泛应用于生命科学的各个领域.二维聚丙烯酰胺凝胶电泳法(2D PAGE)是蛋白质组学核心技术.就蛋白质组学在皮肤病学基础研究和临床皮肤病中的应用进行综述.     

Molecular basis of severe myoclonic epilepsy in infancy

Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies.     

Functioning and disability 6–15 years after traumatic brain injuries in northern Sweden

Objectives –  To assess long‐term functioning and disability after traumatic brain injury (TBI). Material and methods –  Individuals (n = 88) in Norrbotten, northern Sweden, who had been transferred for neurosurgical care were assessed with internationally established TBI outcome measures 6–15 years post‐injury. Results –  There was an improvement in overall outcome from discharge from inpatient rehabilitation to follow‐up. Many individuals had a high degree of motor and cognitive functioning, which enabled them to live independently in their own home without assistance, but there remained a disability related to community reintegration and social participation. This affected their productivity and to some degree their marital stability. The remaining disability and reduced productivity were related to the age at injury and the injury severity. Conclusions –  Our data showed that individuals with a TBI can achieve and maintain a high degree of functioning many years after the injury. Increasing age and a greater injury severity contributed to their long‐term disability.     

Ultrastructural evidence for the uptake of a neurotoxic snake venom phospholipase A2 into mammalian motor nerve terminals

A mutant form of ammodytoxin A, a neurotoxic phospholipase A₂ from the venom of the long nosed viper Vipera ammodytes ammodytes, was prepared by site-directed mutagenesis, conjugated to a nanogold particle and inoculated into the antero-lateral aspect of one hind limb of female mice. Eight hours later the mice were killed, the soleus muscles of both ipsi- and contra-lateral hind limbs were removed, exposed to a silver enhancing medium and then prepared for transmission electron microscopy. Silver-enhanced particles were subsequently found concentrated in the peri-synaptic area, particularly within the synaptic gutter and the deep synaptic folds, and in many cases had been taken up into the cytoplasm of the terminal boutons of the motor axon. The results suggest that the presynaptic neurotoxicity of snake venom phospholipases A₂ involves several components of the neuromuscular apparatus, including intracellular organelles of the motor nerve terminal.